We examined the instability of organ donation decisions made by next-of-kin and factors that predict whether nondonors wish they had consented to donation. Next-of-kin of donor-eligible individuals from one organ procurement organization participated in a semistructured telephone interview. Participants were asked if they would make the same decision if they had to make it again today. Of the 147 next-of-kin donors, 138 (94%) would make the same decision again, 6 (4%) would not consent to donation and 3 (2%) were unsure. Of the 138 next-of-kin nondonors, 89 (64%) would make the same decision again, 37 (27%) would consent to donation and 12 (9%) were unsure. Regret among nondonors was more likely when the next-of-kin had more favorable transplant attitudes (OR = 1.76, CI = 1.15, 2.69), had the first donation discussion with a non-OPO professional (OR = 0.21, CI = 0.13, 0.65), were not told of their loved one's death before this discussion (OR = 0.23, CI = 0.10, 0.50), did not feel they were given enough time to make the decision (OR = 0.25, CI = 0.11, 0.55), had not discussed donation with family members (OR = 0.30, CI = 0.13, 0.72) and had not heard a public service announcement about organ donation (OR = 0.29, CI = 0.13, 0.67). Organ procurement organizations (OPOs) should consider targeting these variables in educational campaigns and donation request approaches.